Autism spectrum disorders (ASD) are increasingly recognized, but the mechanisms that lead to the development of these disorders are poorly understood. With the emergence of improved diagnostic measures and genetic technology, the field has realized that phenotypic heterogeneity is largely due to multiple genes. There are few investigators trained to identify phenotypic differences in behavior and physiology within this broad diagnostic spectrum, and even fewer simultaneously trained to integrate this with the study of genetic underpinnings. The candidate has had structured child psychiatry training and will now expand on her research skills through a unique integration of clinical and basic science. The 5 year training proposal (K23) will permit her to develop into an independent clinical investigator by gaining expertise in measuring clinical and neurochemical subphenotypes as well as applying genetic tools to examine associations. The project described below has been designed to develop relevant research skills to bridge interdisciplinary fields under the mentorship of Edwin Cook, Jr., M.D., a clinical research expert in autism and genetics, and C. Sue Carter, Ph.D., a basic science expert in specific neurohormonal measures that have been shown to vary in autism. The principal investigator will study children with ASD by focusing on clinical phenotype, neurochemical measures and genetic associations of related neuropeptide hormones, including oxytocin (OT) which is currently under trial for ASD treatment. Using an existing sample of patients, the investigator will examine whether genes in the OT and vasopressin (AVP) systems are associated with autism overall, and with specific phenotypic subgroups. She will also conduct a clinical study to test the hypothesis that phenotypic differences in peripheral OT levels are related to allelic variance of specific OT pathway processing genes. Over the 5-year training period, 250 outpatient subjects with ASD, ages 5-18 years, will be recruited for diagnostic, OT/AVP blood assay, and genetic pathway testing. They will be an eligible subset of the 650 patients fully assessed by the University of Illinois at Chicago (UIC) Autism Center of Excellence and Simons Genetics Projects. UIC provides an ideal environment for training given the overlap of multidisciplinary expertise and support to establish a program of research within this highly needed scientific interface.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH082121-04
Application #
8013082
Study Section
Special Emphasis Panel (ZRG1-CPDD-J (02))
Program Officer
Gilotty, Lisa
Project Start
2008-02-07
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$185,370
Indirect Cost
Name
University of Illinois at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Francis, Sunday M; Kim, Soo-Jeong; Kistner-Griffin, Emily et al. (2016) ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR. Front Neurosci 10:516
Francis, Sunday M; Kistner-Griffin, Emily; Yan, Zhongyu et al. (2016) Variants in Adjacent Oxytocin/Vasopressin Gene Region and Associations with ASD Diagnosis and Other Autism Related Endophenotypes. Front Neurosci 10:195
Bishop, Jeffrey R; Najjar, Fedra; Rubin, Leah H et al. (2015) Escitalopram pharmacogenetics: CYP2C19 relationships with dosing and clinical outcomes in autism spectrum disorder. Pharmacogenet Genomics 25:548-54
Ceroni, Fabiola; Sagar, Angela; Simpson, Nuala H et al. (2014) A deletion involving CD38 and BST1 results in a fusion transcript in a patient with autism and asthma. Autism Res 7:254-63
Francis, S M; Sagar, A; Levin-Decanini, T et al. (2014) Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders. Brain Res 1580:199-218
Levin-Decanini, Tal; Maltman, Nell; Francis, Sunday M et al. (2013) Parental broader autism subphenotypes in ASD affected families: relationship to gender, child's symptoms, SSRI treatment, and platelet serotonin. Autism Res 6:621-30
Levin-Decanini, Tal; Connolly, Sucheta D; Simpson, David et al. (2013) Comparison of behavioral profiles for anxiety-related comorbidities including ADHD and selective mutism in children. Depress Anxiety 30:857-64
Hammock, Elizabeth; Veenstra-VanderWeele, Jeremy; Yan, Zhongyu et al. (2012) Examining autism spectrum disorders by biomarkers: example from the oxytocin and serotonin systems. J Am Acad Child Adolesc Psychiatry 51:712-721.e1
Jacob, Suma; Brune, Camille W; Badner, Judith A et al. (2011) Family-based association testing of glutamate transporter genes in autism. Psychiatr Genet 21:212-3
Flores, Cindi G; Valcante, Gregory; Guter, Steve et al. (2011) Repetitive behavior profiles: Consistency across autism spectrum disorder cohorts and divergence from Prader-Willi syndrome. J Neurodev Disord 3:316-24

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